Abstract

Scales measuring positive and negative symptoms in schizophrenia remain the primary mo Scales measuring positive and negative symptoms in schizophrenia remain the primary mode of assessing and diagnosing schizophrenia by clinicians and researchers. The scales are mainly used to monitor the severity of positive and negative symptoms and track treatment response in schizophrenics. Although these scales are widely used, quality as well as general utility of each scale varies. The quality is determined by the validity and reliability of the scales. The utility of the scale is determined by the time of administration and the settings for which the scales can be administered in research or clinical settings. There are relatively fewer articles on the utility of newer scales like CAINS (Clinical Assessment Interview for Negative Symptoms) and the BNSS (Brief Negative Symptom Scale) that compare them to the older scales PANSS (Positive and Negative Symptoms Scale), SAPS (Scale for the Assessment of Positive Symptoms) SANS (the Scale for the Assessment of Negative Symptoms), NSA-16 (Negative Symptom Assessment-16) and CGI-SCH (Clinical Global Impression Schizophrenia. The older scales were developed more than 30 years ago. Since then, our understanding of negative symptoms has evolved and currently there are newer rating scales evaluating the validity of negative symptoms. The older scales do not incorporate the latest research on negative symptoms. CAINS and BNSS are attractive for both their reliability and their concise accessible format, however, a scale that is simpler, accessible, user-friendly, that incorporates a multidimensional model of schizophrenia, addresses the psychosocial and cognitive component has yet to be developed.

Keywords

Introduction

Since Eugen Bleuler coined the term “schizophrenia” in 1908 as a name for what was originally known as “dementia praecox”, schizophrenia continues to be a disorder that remains challenging to define. As can be expected, various scales and instruments have been proposed and developed for both clinicians and researchers to screen for schizophrenia, and these different instruments reflect the different understandings of how schizophrenia can be best defined and classified in terms of its symptoms. Up until the 1980s, most researchers focused on symptoms that could be described as “positive” symptoms, such as hallucinations, delusions, and thought disorders, while generally ignoring apathy, alogia, avolition and other so-called “negative” symptoms. In 1980, however, TJ Crow’s ground-breaking model of schizophrenia as a disease comprised of “two syndromes” introduced the concept of a dichotomous set of positive and negative symptoms and changed much of how researchers would later understand and screen for schizophrenia [1].

Since then, scales developed to screen for schizophrenia have primarily focused on assessing patients through the use of positive and negative symptoms. The PANSS, SAPS, SANS are well-established scales that have been used to objectively assess for schizophrenia symptoms. The fact that it is sensitive to change makes it a “gold standard” in treatment studies. Psycho-pharmacological research supports the PANSS’ construct, discriminative, convergent, and predictive validity, as well as its drug sensitivity, when used longitudinally. The PANSS is not designed to rate negative symptoms exclusively; rather, it is a comprehensive scale for the assessment of psychopathology. Furthermore progress in the development of new pharmacological treatment for the negative symptoms of schizophrenia is restricted by limitations of available assessment tools. The multi-site Collaboration to Advance Negative Symptoms Assessment was established to develop and validate a new clinical rating scale CAINS (The Clinical Assessment Interview for Negative Symptoms) to address limitations of existing measures. To the author’s knowledge, there has not yet been any review article evaluating older scales (for the assessment of positive and negative symptoms of schizophrenia and comparing them with the newer scales (CAINS and BNSS).

Objective

The main objective of this paper is to review and assess utility of well-established scales: the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptoms Scale (PANSS), the Negative Symptom Assessment (NSA-16) and Clinical Global Impression Schizophrenia (CGI-SCH) and to compare these scales to newer screening tools the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS).

Methods

A literature review from 1980-2016 was performed using the following search engines: PubMed, First Search, Cochran, Google scholar online, EBSCO host, and http://psychiatryonline.org. Boolean search terms included “positive symptoms scale in schizophrenia”, “negative symptoms scale in schizophrenia”, “positive and negative syndrome scale in schizophrenia”, “screening for schizophrenia” and “utility of scales in schizophrenia”. Research articles that were generated using the above mentioned search terms met our inclusion criteria if at least one of the negative or positive symptoms scales (PANSS, SANS, SAPS, NAS-16 and CGI-SCH CAINS, BNSS) were mentioned within the title and/or abstract. We excluded editorials.

The scale for the assessment of negative symptoms and the scale for the assessment of (SANS and SAPS)

The Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) were developed in 1980 to fill a conspicuous gap in tools that could effectively measure the severity of negative and positive symptoms [2]. A standardized scale measuring either positive or negative symptoms did not exist at the time, and negative symptoms were often overlooked, in both clinical settings as well as in research, while positive symptoms were sometimes overemphasized. With Crow’s work on the importance of negative symptoms, new interest in screening patients with negative symptoms, as well as the inter correlation of negative symptoms, arose [3]. Partly in response to this paradigm shift, the Scale for the Assessment of Negative Symptoms (SANS) was developed [4].

SAPS were subsequently released a year later, enabling the clinician to evaluate positive symptoms using a similar structure and format to SANS [5]. Specific symptoms in both scales were chosen on the basis of both clinical experience and empirical, statistical evaluation of data interrelationships and correlations [6].

SANS and SAPS are both utilized frequently in clinical and research settings. The question of reliability and validity has been raised since its inception, and various studies have been conducted on the validity of the scales. Earlier studies have mostly focused on inter rater reliability, which has been shown to be consistent, even in multiple cross-cultural settings [2]. Other studies have focused on the temporal stability of the two scales, particularly in regards to the effect of treatment [7]. One study conducted by Malia et al. demonstrated that while SAPS and SANS both show moderate temporal stability over a 12 month time frame, subscale scores of apathy and bizarre behavior were not shown to have much stability [8].

Nature of scoring

The SANS and SAPS are most widely used rating scales were developed in the 1980s. SANS measures negative symptoms on a 25 item, 6-point scale. Items are listed under the five domains of affective blunting, alogia, avolition/apathy, anhedonia/asociality and attention.

While SAPS and SANS are commonly utilized throughout research to assess symptoms of schizophrenia, one pertinent criticism of these two scales strikes at the positive/negative symptoms model of schizophrenia that has been popular since the 1980s. Some have suggested that the bi-dimensional relationship between SAPS and SANS may be confounding the ability of those who use the scales to move beyond a dualistic model of negative and positive symptoms, which in itself may be a construct that is not necessarily helpful Essentially advocating for a reconceptualization of the structure of schizophrenia, Klimidis et al. and Minas et al. [9,10] proposed a multidimensional structure composed of at least three categories, including hallucinations/delusions, positive thought disorder and negative symptoms, rather than merely dividing schizophrenic symptoms into positive and negative symptoms. A separate study conducted by on the inter-correlations between symptoms utilizing SAPS and SANS produced a three dimensional model composed of psychotic, disorganized and negative factors [11]. Proponents of a more complex paradigm of schizophrenic symptomatology argue that schizophrenia cannot be separated or divided as neatly as SAPS and SANS and other earlier models based on Crow’s “two syndromes” work would suggest, and that newer models may need to be developed that take more dimensions, incorporating the diverse elements of schizophrenic symptoms, into their structures.

The positive and negative symptom scale (PANSS)

PANSS provides objective measuring of clinical response to pharmacologic treatments and it is incredibly useful in clinical research, with some claiming it as the “gold standard measure of treatment efficacy”. Longitudinal data for individual patients can be pooled together to examine the effect covariates have on the treatment arm versus the control placebo group in therapy specific studies, hence, PANSS is a reliable means of assessing patients chronologically throughout the course of their illness. A study categorized patients into four mutually exclusive groups based upon results from the PANSS. These results showed that in a treatment group primarily seen in outpatient setting- “19% of individuals were classified as having prominent negative symptoms, 20% as having prominent positive symptoms, and 21% as having both prominent positive and prominent negative symptoms” [12]. The study reinforced that those with negative symptoms have poorer overall outcomes as measured by remission rates and that those with both positive and negative symptoms have even worse outcomes, further demonstrating that the negative symptoms directly affect severity and chronicity of schizophrenia.

In the midst of a body of literature with supportive data on the validity and usefulness of PANSS, some still question the scale’s ability to serve as a “stand-alone” screen for schizophrenia, challenging its reputation for being the gold standard scale. There is a degree of ambiguity and redundancy for evaluation of cognitive items assessed through its sub-scales. The biggest pitfall of PANSS is its lack of sensitivity and specificity in predicting global cognitive functioning. Additionally, the depression sub-scale fails to differentiate between “depression, negative symptoms, and extra-pyramidal side effects” which is a crucial problem given the distinct treatments and adverse downstream sequelae if inappropriately diagnosed [13]. Evaluating the factors measured by PANSS individually in a comprehensive fashion often leads to creating lengthier scales with redundant inquiries. Conversely, however, paring down the scale to minimal inquiries is just as problematic and can result in yielding incomplete data, weaker correlations, and less reliable outcomes [13]. Also, studies that use the PANSS to evaluate the efficacy of psychotropic pharmacotherapy can be biased when mean outcomes are reported, serving as a systematic flow that is unlikely to detect covariates affecting placebo response [13].

Indeed, one of the most common drawbacks of PANSS is its complexity. In addition to its length, PANSS, which utilizes an interval scale of 1 to 7 for each of its 30 items, requires converting PANSS into a ratio scale in order to score patients and track response to treatment correctly. A recent systematic review found that as many as 62% of authors utilizing PANSS may have used incorrect calculations in their research, and that very few of the articles even included calculation methods [14].

PANSS was consistently better when directly compared to an older counterpart, the Brief Psychiatric Rating Scale (BPRS), in a psychiatric rehabilitation study with 154 concurrent ratings. Both tools exhibited strong inter rater reliability; however, the study showed that PANSS was superior to the BPRS in clinical predictive power [14].

Negative symptoms assessment 16 (NSA-16)

The original NSA-26 scale was developed by Alphs et al. in 1989 [15]. The newer truncated version, the Negative Symptoms Assessment-16 (NSA -16) was adapted from the prototype by in 1993 is a validated tool for evaluating negative symptoms of schizophrenia [16]. The NSA-16 examines for the presence, severity and range of negative symptoms associated with schizophrenia. It was meant to be a concise and easy-to-use instrument with strong psychometric properties in terms of validity, reliability, sensitivity to change and good clinical utility.

The NSA-16 is a semi-structured interview containing 16 items that comprehensively assess the negative syndrome of schizophrenia and it includes the following factors: communication, emotion/affect, social involvement, motivation and retardation [15]. These factors are assessed through a structured interview and are extensive and welldefined to help standardize assessment [16].

Axelrod et al. [16] assessed the validity of this scale in a sample of 223 un-medicated schizophrenic inpatients sample. In this study, a five factor model was found to best characterize the structure of this rating scale. The study provided support for a multidimensional model of negative symptoms in schizophrenia and it offered a useful measure of negative symptoms assessment. Standardized measurement of negative symptoms was also achieved in international trials, further supporting the validity of NSA-16. Dawn Velligan et al. examined whether changes in negative symptoms (NSA 16) were associated with changes in functional outcome. Results showed that the relationship between negative symptoms changes and change in functional outcome is complex and that negative symptoms drove the changes in the social and occupation functional scale (SOFAS) rather than reverse [17].

Nature of scoring

It is a semi-structured 16 items interview, utilizing the 5-factor 1. Communication; 2. Emotion/Affect; 3. Social Involvement; 4. Motivation; 5. Retardation [18]. Items are rated using a 6-point Likert scale where higher scores reflect greater impairment. Detailed anchoring criteria for the rating points are provided in the scale, along with a total score, sum of the scores on the 16 items and a global negative symptom rating based on the global clinical impression of the patient’s negative symptoms [19].

Criticism

The main limitation of the NSA is its high reliance on functioning or behaviors even for experiential symptoms such as reduced social drive whose severity is measured by type and frequency of social interactions [19]. The SANS and the NSA-16 both provide a focused assessment of negative symptoms, but they must be used in conjunction with a positive symptom rating scale [18].

Negative symptoms assessment 4 (NSA-4)

A study published in Int. J of Psychiatry about the validation of a 4- item Negative Symptom Assessment (NSA-4). This study revealed NSA-4 is a short, practical clinical tool for the assessment of negative symptoms in schizophrenia. The psychometric properties and predictive power of a four-item version (NSA-4) were compared with the NSA-16 to determine predictive validity and construct validity. Both scales showed acceptable internal consistency (cronbach alpha 0.85 and 0.64, respectively) and test retest reliability (intra-class correlation coefficient 0.87 and 0.82). This study demonstrates that NSA-4 offers accuracy comparable to the NSA-16 in rating negative symptoms in patients with schizophrenia [20].

Two studies examined whether changes in negative symptoms, as measured by scores on the 16-item Negative Symptom Assessment scale (NSA-16), were associated with changes in functional outcome. Findings from these studies indicate that the relationship between negative symptom change and the change in functional outcomes is complex, and points to potential issues in selection of assessments [15,17].

CGI-SCH scale (The Clinical Global Impression- Schizophrenia Scale)

The CGI-SCH scale assesses the positive, negative, depressive, and cognitive symptoms and overall severity in schizophrenia [21]. The Clinical Global Impression-Schizophrenia (CGI-SCH) scale is a brief assessment instrument which is originally adapted from the Clinical Global Impression (CGI) scale [22] and the CGI-Bipolar Patients (CGI-BP) scale [23]. It was developed to study the outcome of antipsychotic treatment in schizophrenia in an observational study (Schizophrenia Outpatient Health Outcomes (SOHO) Study [24].

The CGI-SCH has shown strong validity and it has slightly higher interrater reliability than that for the PANSS [25]. In a study of 114 patients to measure the diversity of symptoms present in schizophrenia found high correlation coefficients between the CGI-SCH, Global Assessment of Function (GAF) and PANSS scores and substantial reliability in all dimensions except depressive dimension. This study concluded the CGI-SCH scale is a valid, reliable instrument to evaluate severity and treatment response in schizophrenia. There is stronger support for positive, negative, cognitive and global rating rather than depressive symptoms. It is a simple, concise and quick to administer instrument which makes it an appropriate scale for use in observational studies and routine clinical practice [21].

Nature of scoring

The CGI-SCH is simpler scales as it consists of only two categories; severity of illness and degree of change. The severity of illness category evaluates the situation during the week previous to the assessment, while the degree of change category evaluates the change from the previous evaluation. Each category contains five different ratings (positive, negative, depressive, cognitive and global) that are evaluated using a seven-point ordinal scale.

In 2005, the National Institute of Mental Health held a consensus development conference on negative symptoms .Two next-generation negative symptom scales resulted from this meeting: BNSS and CAINS. Both measures are becoming widely used and various research studies have demonstrated good psychometric properties for each scale. The study published in schizophrenia bulletin provides the first direct psychometric comparison of these scales. In this study 65 outpatients patients diagnosed with schizophrenia or schizoaffective disorder that completed clinical interviews, questionnaires and neuropsychological testing. Separate raters completed the BNSS and CAINS within the same week. Results indicated that both measures had go`od internal consistency, convergent validity, and discriminate validity. High correspondence was observed between CAINS and BNSS blunted affect and alogia items. Moderate convergence occurred for avolition and asociality items, and low convergence was seen among anhedonia items. Findings from this study suggest that both scales have good psychometric properties [26].

The CAINS is an effective and validated tool for measuring negative symptoms in schizophrenia, Using a diverse sample of 162 outpatients with schizophrenia or schizoaffective disorder, the researchers assessed the structure, interpreter agreement, test-retest reliability, and convergent and discriminant validity of the 13-item tool. Results were promising. The scales demonstrated good internal consistency, testretest stability, and interrater agreement. The CAINS also showed strong convergent validity, which was determined by linkages with other measures of negative symptoms. CAINS- though it’s brief yet comprehensive and employable across a wide range of research and clinical contexts [27].

A study published in Schizophrenia research highlighted the fact patients with schizophrenia, those who have persistent and clinically significant negative symptoms (PNS) have the poorest functional outcomes and quality of life [28]. The presence of negative symptoms represents an unmet therapeutic need for large numbers of patients with schizophrenia. There is not any psychosocial treatment model have been established which could addresses the entire constellation of PNS. In this study total 51 patients with PNS were randomized into one of two groups for a period of 9 months: 1) MOtiVation and Engagement (MOVE) or 2) Treatment as usual. MOVE was a home based multi-modal treatment that employed a number of cognitive and behavioral principles to address the broad range of factors contributing to PNS and their functional consequences. Patients were assessed at baseline and every three months with multiple measures of negative symptoms. The results from this study revealed repeated measures analyses of variance for mixed models indicated significant Group by Time effects for the Negative Symptom Assessment (NSA; p<0.02) and the Clinical Assessment Interview for Negative Symptoms (CAINS p<0.04). Group differences were not significant until nine months of treatment and were not significant for the Brief Negative Symptom Scale (BNSS) [28].

According to 2005 NIMH–MATRICS consensus statement, CAINS and BNSS both scales address the five currently recognized domains of negative symptoms, differentiate appetitive from consummatory aspects of anhedonia and address desire for social relationships. Thus far, both have exhibited promising psychometric properties [29].

The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings from previous research studies indicate that the CAINS are brief yet comprehensive and employable across a wide range of research and clinical contexts. Negative symptoms are resistant to treatment and impede functional recovery in schizophrenia. Recognizing the clinical importance of negative symptoms, the top recommendation of the Consensus Development Conference on Negative Symptoms (convened by the National Institute of Mental Health (NIMH) and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS initiative) for stimulating novel treatment development [27].

Nature of scoring

The CAINS and BNSS are two scales that explore psychometric domains including negative symptoms, different aspects of anhedonia and interest in social relationships with others. Both scales use 13 items to assess negative symptoms [27]. It is anticipated that prospective clinical trials enrolling those with negative symptoms will demonstrate the relative sensitivity to change and global suitability of the BNSS and CAINS vs. each other and the earlier generation scales [30]. Hence, multiple studies have found that regardless of the scale used to assess negative symptoms, strong correlations exist between higher negative symptom scores and poorer social functioning [27,28,30].

Criticisms

Although, CAINS and BNSS are attractive for both their reliability and their concise, accessible format. However, CAINS and BNSS continue to evaluate patients primarily diagnosis on the basis of negative symptoms, with no integration of other aspects of the patients’ social and cognitive functioning. The common critique leveled at SAPS and SANS for being too restrictive can also be applied to both CAINS and BNSS, and multidimensional scales has yet to be developed. Furthermore CAINS scales are not strongly related to depression, agitation or positive symptoms [27].

Conclusion

The older scales were developed more than 30 years ago. Since then, our understanding of negative symptoms has been evolved and currently we have newer rating scales reviewing the validity of negative symptoms. The older scales questionnaire does not incorporate the latest research on negative symptoms established by the NIMH consensus development conference on negative symptoms (CAINS and BNSS). This is the biggest difference between the older and newer scales. Although, CAINS and BNSS are attractive for both their reliability and their concise, accessible format. However, CAINS and BNSS continue to evaluate patients primarily diagnosis on the basis of negative symptoms, with no integration of other aspects of the patients’ social and cognitive functioning.

It is clear that the newer negative symptom scales represent progress in the understanding of schizophrenia psychopathology. However; they still neglect to address the psychosocial and cognitive factors that are useful outcome measures.

While there are many different scales available to assess positive and negative symptoms of schizophrenia, a scale that is simpler, accessible, user-friendly and that incorporates a multidimensional model of schizophrenia, address the psychosocial and cognitive deficit component yet to be developed to better understand severity and psychopathology of schizophrenia.